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Background Automated insulin delivery is a game changer for type 1 diabetes treatment. Objective To describe the benefits of automated insulin delivery in a specific complex setting. Methods We are herein presenting a case of a patient with type 1 diabetes, in which Hybrid Closed Loop (Medtronic Minimed 670G on Auto Mode) was used over a year during automated peritoneal dialysis. The patient was previously on insulin therapy with sensor augmented pump and we switched him to Hybrid Closed Loop shortly before the begin of dialysis. Results Automated insulin delivery produced an increase of time in range (70-180 mg/dl) from 63% to 72%, after 3 months and to 74% after one year. Moreover, no hypoglycemia/hyperglycemia urgencies occurred overall during the year. Conclusions The case detailed here is the first report of Hybrid Closed Loop in a patient on automated peritoneal dialysis and it shows an improvement of time in range with a satisfying safety profile in a fragile, aged patient.

The 2019 ESC-EASD guidelines provide recommendations for CV risk assessment and medical treatment in diabetic patients. Three CV risk categories were originally defined: 1) very high risk, 2) high risk and 3) moderate risk according to the presence of CVD, other target organ damage (proteinuria, renal impairment defined as eGFR ≥ 30 mL/min/1.73 m2, left ventricular hypertrophy, retinopathy), duration of disease, age, risk factors (hypertension, dyslipidemia, smoking, obesity). In very high risk CV category SGLT2-I and GLP1-RA were identify as treatment of choice. Based on these criteria, we developed the web APP “AWARE”, an application software which runs on a web server and is accessed via internet browser. From November 10th 2020 to January 10th 2021 we employed AWARE as a tool to assess CV risk of 650 type 2 diabetes patients in clinical practice. The APP was implemented with additional features such as HbA1c and therapy. Of the 650 subjects examined, 430 were very high risk (66%), 73 (11,2%) high risk, 5 (0,8%) at moderate risk while 145 patients (22%) didn’t match with any of these categories. We allocated these patients into an additional “undetermined risk” category. Median HbA1c in all subjects was 7.2±1.14 (7,3±1.15% in very high risk category, 7.2±1.15% in high risk category, 6,2±0.41% in moderate risk and 6.9±1.12% in “undetermined” risk). In the very high risk category CVD was present in 166 subject (38%), duration of disease>10 aa in 238 subjects (55%), proteinuria in 53 subjects (12%) (p=0.000 vs. all other categories). Either SGLT2-I or GLP1-RA were prescribed in 30% of patients in the very high risk category. The APP “AWARE” in useful to identify CV risk in diabetic. The classification according to the criteria of 2019 ESC/EASD guidelines does not includes 22% of patients in clinical practice. Around 70% of patients in the very high CV risk category are not treated with the optimal drug therapy suggested by the 2019 ESC/EASD guidelines. Disclosure C. C. Berra: None. R. Manfrini: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Mundipharma International, Novo Nordisk, Sanofi. R. Ghelardi: None. P. M. Bollati: None. L. Bucciarelli: None. M. Mirani: None. M. Muratori: None. F. Folli: None. Aware study group: n/a.

Hyperthyroidism is characterized by hyperadrenergic symptoms (i.e., tachycardia, anxiety, and increased metabolic state). Although hyperthyroid patients often complain about an impairment of sleep, no data are available on sleep characteristics and autonomic cardiovascular control during sleep in these patients. We aimed to assess sleep qualitative indices and autonomic cardiovascular regulation during sleep in hyperthyroidism (Hyperthyr) and after treatment. Six subjects with a first diagnosis of Graves’ disease or hyperfunctioning nodule underwent a complete polysomnographic study (PSG) at the time of diagnosis and after the treatment, when they became euthyroid (Euthyr). ECG and respiratory signals were extracted and samples of consecutive 250–300 beats were analyzed using linear spectral and nonlinear entropy analysis of heart rate variability (HRV), during the different sleep stages. Heart rate was decreased and total power increased in Euthyr compared to Hyperthyr, both during wake and sleep; no changes of the sympathovagal balance were observed. Entropy analysis showed that regularity index was reduced in Euthyr compared to Hyperthyr, suggesting changes in the complexity of the cardiovascular control. Periodic leg movements (PLM) were reduced in Euthyr compared to Hyperthyr. In conclusion, hyperthyroidism seems to be associated with an increased sleep fragmentation, due to PLM and an altered cardiac autonomic control.

In order to verify whether synthetic peptide histidine methionine (PHM-27) is able to induce serum prolactin (PRL) rise in normal subjects and to investigate its effect on PRL secretion in hyperprolactinemic conditions, PHM-27 (100 micrograms i.v. over 60 min at a rate of 3.3 micrograms/min) was given to 6 normal subjects and 11 hyperprolactinemic women, and serum PRL levels were measured before and at intervals up to 120 min after beginning the infusion. On a separate occasion, a saline infusion was administered to all these subjects as a control test. In normal subjects, PHM-27 caused PRL to increase from 7.8 +/- 1.4 micrograms/l (mean +/- SE) to 13 +/- 2.1 micrograms/l (p < 0.05), the peak occurring at 30 min, whereas it did not significantly modify serum PRL levels in 11 patients with prolactin-secreting adenomas. We also observed a significant difference of serum PRL pattern during PHM infusion when compared to saline in normal subjects. In contrast, in hyperprolactinemic states, PRL curves were similar in both tests. Continuous infusion of PHM-27 was very well tolerated and caused no important adverse events. These data suggest that PHM, like vasoactive intestinal peptide, can participate in the regulation of PRL release under physiological conditions and that the unsignificant PRL increase in PRL-secreting tumors may reflect abnormalities of the PRL secretion mechanism in these pathological states.

Osteocalcin (OC) concentration, a specific index of bone formation, was measured in 29 female patients with microprolactinoma (serum prolactin, PRL: 105 ± 10.9 ng/ml; mean ± SE). Mean OC levels were significantly lower than in controls (1.7 ± 0.2 vs 5.1 ± 0.3 ng/ml; p < 0.001), being below the normal range in 28 out of 29 patients. All patients were treated with dopaminergic agents (dihydroergocriptine, bromocriptine or cabergoline). After treatment mean serum PRL levels were significantly reduced (12 ± 3.1 ng/ml; p < 0.001), a full normalization being obtained in 26 patients. There were no significant differences in both basal and after treatment PRL levels among patients treated with different drugs, although a greater PRL decrease was induced by cabergo-line. Serum OC levels significantly increased after 12 month therapy (4.7 ± 0.6 ng/ml, p < 0.001), a normal concentration being reached in 14 of 29 cases. During treatment there were no significant differences in serum estradiol and PRL concentrations between patients who normalized or not their OC levels, while the reduction in PRL levels with respect to baseline was more pronounced in the former group. The absolute increase in OC levels positively correlated with serum PRL decrements (p < 0.01). It is noteworthy that serum OC normalized in 1/10 patients during dihydroergocriptine, 3/8 during bromocriptine and 10/11 during cabergoline. Four patients, previously treated with dihydroergocriptine and bromocriptine without normalizing OC and PRL levels, underwent a second course of therapy with cabergoline and then normalized OC concentrations. In conclusion, these preliminary data show that i) OC levels are reduced in women with microprolactinoma, ii) after successful treatment of hyperprolactinemia a recovery of osteoblastic activity frequently occurs. Further investigations on the actions of dopaminergic drugs are needed, in view of their different effects on OC concentrations. Tresented in part at the 7th International Congress on calciotropic hormones and calcium metabolism, Salsomaggiore, Italy, October 1988.

Cabergoline (Cab), a very potent and long-lasting dopaminergic compound, was administered to 26 women with pituitary microprolactinoma [mean serum PRL levels: 124.8 +/- 11.3 micrograms/l (+/- SE), range 62-300 micrograms/l] and 3 patients with GH-secreting pituitary adenoma (2 with associated PRL hypersecretion) for 12 and 24 months, respectively. In microprolactinomas, a stable normoprolactinemia was achieved in 96.1% of cases: in 13 women (50%) with the lowest dose of the drug (0.5 mg/week), and in other 12 patients (46.1%) with increasing doses up to 3 mg/week. All the oligomenorrheic/amenorrheic women, except one, restored regular and ovulatory menses. Two patients became pregnant. Pituitary abnormalities at high resolution-CT (HR-CT) scan disappeared in 13 of 19 patients (68.4%) after 12 months of therapy and this feature persisted in 8/13 cases (61.5%) 12 months after drug withdrawal. During Cab discontinuation (range: 3-60 months), mean serum PRL levels remained significantly lower than the basal ones. Six of 25 women are still without therapy. In 2 patients, normoprolactinemia persisted up to 38 and 60 months, respectively. Cab treatment was re-instituted in 13 patients because of the recurrence of hyperprolactinemia. Five patients were lost at follow up. In all the acromegalic patients, Cab (1-3 mg/week) normalized serum GH, IGF-I and PRL levels. A clear improvement in clinical symptoms was observed in all patients, but neuroradiological improvement in only one. Cab therapy was very well tolerated, as only seven patients complained of mild and transient side-effects and none had to stop treatment. In conclusion, Cab is an effective, safe, and well tolerated dopaminergic compound for the treatment of hyperprolactinemic disorders and the control of the clinical and hormonal features of dopamine-sensitive acromegalic patients.

The effects of dihydroergocriptine (DHECP), a dihydrogenated ergot alkaloid with dopaminergic agonistic and alpha-adrenergic antagonistic properties, were studied in 22 women with PRL-secreting microprolactinomas and compared with those recorded in 36 previously studied patients treated with bromocriptine (BRC). After acute administration of 5 mg DHECP, orally, serum PRL decreased by 61 +/- 18% (+/- SD); only 1 patient was unresponsive. The nadir was reached at 300 min. Long term treatment with increasing DHECP doses caused a progressive PRL fall from 125 +/- 142 (+/- SD) to 81 +/- 159 micrograms/L after 1 week of a 3 mg twice daily regimen, to 64 +/- 88 micrograms/L after 1 week of 5 mg twice daily, 46 +/- 57 micrograms/L after 1 week of 10 mg twice daily, and 28 +/- 34 to 33 +/- 45 micrograms/L throughout 9 months of treatment with 10 mg DHECP 3 times daily. Seventy-seven percent of patients had normal serum PRL levels during chronic treatment. All women, including those with supranormal serum PRL levels, resumed regular menses, and 16 had ovulatory cycles; 1 woman became pregnant. Galactorrhea disappeared in all. During treatment the PRL response to TRH, initially absent in all patients, became positive in 10. In 7 patients, after DHECP treatment for 9 months, high definition computed tomographic scan no longer showed the focal lesions initially seen. After drug withdrawal, serum PRL increased again in all except 1 patient. Two patients had regular menses for 6 months, and 3 still had no adenoma imaged by high definition computed tomography. In BRC-treated patients the serum PRL changes and clinical results were very similar to those in the DHECP-treated patients, except for the persistence of normal serum PRL levels in 4 patients after drug withdrawal. On the other hand, side-effects were negligible during DHECP treatment, but remarkable during BRC. Systolic and diastolic blood pressures decreased by only 5.4 and 3.0 mm Hg, respectively, after acute 5 mg DHECP administration, but decreased by 12.8 and 14 mm Hg after acute 2.5 mg BRC administration. Orthostatic hypotension and peripheral vasomotor phenomena occurred in the long term DHECP treated patients except one, but they occurred in 9 and 3 of those treated with BRC, respectively. Gastric discomfort or mild nausea occurred in 12 DHECP-treated patients, while mild or severe nausea or vomiting were observed in 18, 11, and 2 of those taking BRC, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

In order to investigate the influence of dopamine (DA) in modulating prolactin (PRL) response to vasoactive intestinal polypeptide (VIP), VIP (75 micrograms i.v. over 12 min) was administered to normal women and patients with microprolactinomas during saline or DA (0.06 micrograms/kg BW/min) infusion. In 8 normal women VIP caused PRL to rise from 7.9 +/- 0.8 (mean +/- SE) to 33.4 +/- 17.1 ng/ml (p less than 0.01), the peak occurring at 15 min, while it did not elicit any significant modification in serum PRL levels in 18 patients with microprolactinomas. DA infusion lowered serum PRL by 67 and 58.2% at 120 min in normal women and in patients with microprolactinomas, respectively, and abolished VIP-induced PRL response in normal women without influencing PRL response in patients with microprolactinomas. PRL responsiveness to VIP was not restored by dopaminergic disinhibition (domperidone 10 mg i.v.) in 4 patients tested. Two previously unresponsive patients showed a VIP-induced PRL increase, superimposable on that recorded in normal women, after successful selective adenomectomy. These data suggest that DA, although able to suppress VIP-induced PRL response in normals, does not play any major role in causing unresponsiveness to VIP in prolactinomas. The lack of PRL responsiveness to VIP might be intrinsic to the adenoma or due to alterations of PRL secretion regulatory mechanisms other than DA secondary to the presence of the tumor, or to a depletion of the readily releasable pool of PRL.

Hyperthyroidism is a pathological condition characterized by an altered autonomic cardiovascular control, resulting in an increase of the sympathetic and a decrease of the parasympathetic modulation of heart rate variability. Recently, the entropy-based indices derived from short-term heart period variability have been proved to be helpful in evaluating the autonomic cardiovascular modulation. The aim of our study was to evaluate the autonomic cardiovascular modulation of hyperthyroid subjects at rest and during standing using spectral parameters and corrected conditional entropy indices derived from short-term heart period variability in 12 hyperthyroid (HYPTH) and 9 normal healthy (N) females. Mean heart period was significantly decreased by standing both in N and HYPTH and the LF power expressed in normalized units was increased. The respiratory rate was faster in the HYPTH group compared to N and complexity was significantly greater in HYPTH compared to N during standing. Results suggested an enhanced complexity of cardiovascular control in HYPTH, more evident in a condition of sympathetic activation. The increased complexity of the cardiovascular regulation is probably not completely due to autonomic control but also to other influences, such as metabolic effects of thyroid hormones impinging upon respiratory control mechanisms and, therefore, on cardiorespiratory coupling.